Department of Neurosurgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, Fuzhou, China.
J Gene Med. 2024 Aug;26(8):e3724. doi: 10.1002/jgm.3724.
New targeted drugs about angiogenesis could develop the treatment of glioma. We aimed to explore the role of phosducin like 3 (PDCL3) in angiogenesis of glioma.
RNA sequencing data and matched clinical data were downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. To screen for the reliable genes with the filtering analyses, survival, multivariate Cox, receiver operating characteristic (ROC) curve filtration, and clinical correlation analyses were performed. The PDCL3 gene was validated by immunohistochemistry as a reliable gene for further analysis. Then we used the combined data of TCGA and Genotype-Tissue Expression from UCSC to detect the differential gene expression of PDCL3. Related signal pathways in glioma were explored by the gene set enrichment analysis and co-expression analysis. Lastly, we performed in vitro experiments to verify the gene functions and related mechanisms.
The three filtering analyses and immunostaining indicated that the expression of PDCL3 in glioma tissues was higher than the normal tissues. Gene function analysis showed that PDCL3 activated the vascular endothelial growth factor (VEGF) signal pathway, and its mechanism was related to pathways in cancer, like NOD like receptor signaling pathway, the RIG-I like receptor signaling pathway and the P53 signaling pathway by MAPK/AKT in gliomas. This suggested that the proliferation, migration and invasion of glioma cells might be inhibited by the downregulation of PDCL3 in vitro, which may be related to the activation of VEGF signaling pathway.
We demonstrated that PDCL3 could function as an independent adverse prognostic marker in glioma. Its pro-oncogenic mechanism may be related to the VEGF signaling pathway.
新的抗血管生成靶向药物可以改善胶质瘤的治疗效果。本研究旨在探讨磷蛋白样 3（PDCL3）在胶质瘤血管生成中的作用。
从癌症基因组图谱（TCGA）和中国脑胶质瘤基因组图谱（CGGA）数据库下载 RNA 测序数据和匹配的临床数据。通过生存分析、多变量 Cox 分析、受试者工作特征（ROC）曲线分析和临床相关性分析进行可靠基因的筛选。采用免疫组织化学法验证 PDCL3 基因的可靠性，并进一步分析。然后，我们利用 TCGA 和 UCSC 基因型-组织表达数据库联合检测 PDCL3 的差异基因表达。通过基因集富集分析和共表达分析探讨胶质瘤中相关信号通路。最后，我们进行了体外实验以验证基因功能和相关机制。
三种筛选分析和免疫组化结果表明，PDCL3 在胶质瘤组织中的表达高于正常组织。基因功能分析表明，PDCL3 激活了血管内皮生长因子（VEGF）信号通路，其机制与 NOD 样受体信号通路、RIG-I 样受体信号通路和 MAPK/AKT 通路有关，在胶质瘤中激活 P53 信号通路。这提示体外下调 PDCL3 可能抑制胶质瘤细胞的增殖、迁移和侵袭，这可能与 VEGF 信号通路的激活有关。
我们证实 PDCL3 可作为胶质瘤的独立不良预后标志物。其致癌机制可能与 VEGF 信号通路有关。
